Arcturus Therapeutics Holdings Inc.

Good day and welcome to the Arcturus Therapeutics Second Quarter 2022 Financial Update and Pipeline Progress Call. Today's conference is being recorded. At this time, I would like to turn the conference over to Kyle Goodstat. Please go ahead, sir.

Thank you, Sarah. Good afternoon and welcome to Arcturus Therapeutics Second Quarter 2022 Financial Update and Pipeline Progress Call. Thank you all for joining us. Today's call will be led by Joseph Payne, our president and CEO, and Andy Sassine, our CFO. Dr. Pad Chivakula, our CSO and COO, will join in for the Q&A session. Before we begin, I would like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by the statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the risk factors section in our Forms 10-Q and 10-K filed with the SEC. Any forward-looking statements represent our views only as of the date such statements are made, August 9, 2022. Arcturus specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances. With that, I'll now turn the call over to Joe.

Thank you, and good afternoon to all. Thank you for joining Arcturus' Q2 quarterly call. My comments today will begin with a brief summary of the business case for our vaccine platform, followed by highlighting our recent progress on our pipeline, including additional details per program, before I turn the time over to Andy for financial updates. The business case for our vaccine platform continues to mature and gain momentum. We begin by re-emphasizing our low dose level. A lower dose level of only 5 micrograms potentially means improved safety benefits and higher manufacturing related profit margins. Our vaccine platform is also devoid of an adjuvant and therefore captures all of the potential safety benefits and manufacturing simplicity associated with that. In addition to the low dose of 5 micrograms and the simplicity of zero adjuvant, our vaccine platform utilizes Arcturus' lyophilization technology. We've now collected impressive cold chain data showing favorable stability, shipping, and storage advantages that our lyophilized vaccines have relative to frozen liquid vaccines. Some of the critical challenges with presently approved COVID vaccines are related to durability and broad spectrum neutralizing antibody activity, especially with respect to the Omicron variants. We believe that Broadly acting and the potentially longer lasting self-amplifying mRNA booster vaccinations would further strengthen our business case for this platform. Indeed, the data we shared today in our press release continues to suggest that self-amplifying mRNA vaccines may be a superior next generation mRNA vaccine technology platform. I will get to more details pertaining to that data shortly. This quarter has been highlighted by several key achievements including significant progress advancing our pipeline of mRNA-based vaccines and therapeutics. Let's begin with ARCT154. This is our self-amplifying mRNA COVID vaccine candidate that has shown impressive activity against SARS-CoV-2 both as a primary vaccine and as a booster. Given the continued widespread circulation of SARS-CoV-2 and the anticipation of a long-term endemic phase. We continue to aggressively move forward with development of ARCT154 as a booster vaccine. We're pleased with the favorable results that continue to come from the ongoing Phase 1-2 study, evaluating 154 in the U.S. and Singapore, given as a 5-microgram booster dose approximately five months after primary vaccination with Comirnaty. The boost with ARCT 154 generated robust neutralizing antibody responses that are sustained through three months after booster vaccination. The neutralizing antibody responses to the parent strain of the vaccine, also known as D614G, and the antibody responses against a panel of SARS-CoV-2 variant strains have also consistently demonstrated antibody responses that have remained elevated over three months. Now moving our attention to the present and more relevant Omicron variants. We are happy to share new data today from the ongoing analysis of this study demonstrating durable immune responses to both Omicron BA.1 and BA.2 variants. Against BA.2, we saw a 39-fold increase in neutralizing antibody titer at day 91 over baseline. This was complemented by a 44-fold increase in neutralizing antibodies against BA.1 at day 91. With these encouraging data, we have growing confidence in ARCT154's profile as a booster vaccine. These data suggest that the broadly immunogenetic low dose and well-tolerated features of our self-amplifying mRNA vaccine platform may compete effectively in a booster market currently dominated by vaccines with narrow SARS-CoV-2 protection and waning immunogenicity and at considerably higher doses. Arcturus is presently collecting six-month booster immunogenicity data for all relevant Omicron variants, including BA.5. We look forward to seeing that data soon and sharing it with our potential strategic commercial partners. Earlier this year, we learned from our collaborator, VinBiocare, that the ARCT154 Phase 1-2-3 study had met its primary endpoint objective of vaccine efficacy. The study demonstrated very strong protection against severe and fatal COVID disease, even when up against the more challenging variants that have escaped other vaccines. Supported by these collected data and the favorable results of the Vietnam Vaccine Efficacy Trial, We have been in discussions with major regulatory agencies, including the FDA, the MHRA, and EMA, regarding the path to pivotal trial and future approval as a booster. Now, based on additional health authority guidance, the booster trial that was slated to start in Q3 has now been split into two smaller and more time and cost-efficient trials, the first of which is expected to start in Q4. The updated study designs are intended to support global registration of ARCT 154 as a booster. The Vietnam Ministry of Health is undergoing a significant reorganization resulting in a delay of the ARCT 154 EUA or Emergency Use Authorization for the primary series. During this reorganization, the MOH or Ministry of Health communicated that the clinical section review is complete and adequate. The MOH provided comments to the CMC section, and this is the chemistry manufacturing and control section, requesting three manufacturing runs to support full market authorization. ARCT 154 is now expected to receive EUA in Q4 2022 with full marketing authorization anticipated in early 2023 if booster studies meet non-inferior immunogenicity and safety objectives. Now the new stability data that was highlighted in our press release today supported the advantages of using a lyophilized vaccine powder to mitigate the cold chain challenges associated with frozen liquid mRNA vaccines. Our lyophilized COVID vaccine powder demonstrated room temperature stability for four days. That's 25 degrees centigrade in the presence of 60% relative humidity. and refrigerator stability for six months, that's 2 to 8 centigrade, and a predicted long-term stability at minus 20 centigrade for 18 months. Transportation in the summer and winter months can provide temperature cycling challenges in the supply chain. This is where liquid products can be frozen or thawed unintentionally, as you can appreciate. And importantly, the lyophilized vaccine powder was not impacted by multiple temperature cycling stresses going from minus 20 to refrigerated temperatures like two through eight or room temperature and vice versa. This enables global shipping logistics and the supply of a stable usable solid COVID vaccine product at two to eight centigrade. Taking these significant cold chain advantages into context with our low dose level, potential durability and broader spectrum of activity compared to conventional mRNA, our next-gen self-amplifying mRNA platform continues to differentiate itself. Our self-amplifying mRNA influenza vaccine has continued its preclinical work. We expect to make a final decision of our lunar flu development candidate this year. Given the comparative speed of mRNA vaccine production, and precise antigenic matching against circulating influenza strains, this is expected to offer an important improvement over currently marketed flu vaccines. Comparatively lower dose, we believe that our approach may be differentiated in other meaningful ways as well. Now I'd like to shift from our vaccine franchise over to our therapeutic mRNA pipeline programs, which continue to advance. I'll begin with an update on ARCT810. This is our therapeutic candidate for ornithine transcarbamylase deficiency or OTC deficiency. OTC deficiency is a result of a urea cycle disorder. It's rare, it's serious, has no approved treatments that address the root cause of the disease. And our approach aims to augment the deficient OTC enzyme in the liver of these patients. ARCT810 has the potential to restore urea cycle activity, prevent or slow the progression of neurological damage and potentially expand dietary options and improve on the quality of life for people living with this condition. We've obtained approval from the United Kingdom's HRA or Health Research Authority and other European authorities to initiate a phase two multiple dose clinical trial for ARCT 810 designed to enroll 24 adolescents and adults. As many can appreciate, it is often challenging to find and identify rare disease patients. We are pleased to report that Arcturus has identified several dozen patients at multiple sites in the United Kingdom, Spain, and Belgium, with France and other countries soon to follow. We plan to screen and dose patients throughout the remainder of this year, with the goal of obtaining interim proof of concept data by year end. We're pleased to report that ARCT 810 was recently granted orphan drug designation by the European Commission for the treatment of Ornithine Transcarbamylase Deficiency. There are key incentives associated with this designation that include reduced regulatory fees for protocol assistance and marketing applications, the use of the centralized marketing authorization procedure, and 10 years of market exclusivity. This European designation complements the orphan drug designation by the US FDA that this program has already received previously. We have also completed dosing of the second cohort of our ascending dose phase 1b study in the US, wherein the participants received a dose of 0.3 milligrams per kilogram of ARCT A10. The Study's Data Safety Review Committee, or DSRC, has recommended continuation of the study and escalation to a higher dose cohort, which will begin dosing imminently. Moving now to our Cystic Fibrosis Program, we've continued to progress the necessary preclinical and non-clinical studies to enable ARCT 032 to move to the clinic. ARCT 032 is our inhaled messenger RNA therapeutic for cystic fibrosis. We recently presented at the European CF Conference in Rotterdam and had a productive update meeting with the CF Foundation, our supportive collaboration partner for this program. And we anticipate the submission of a clinical trial application or CTA for ARCT 032 in Q4 2022. Well, with that, I will now pass the call on to Andy Sassine, our CFO, to provide financial updates.